William Ray Cyrus was born on August 25, 1961 in Flatwoods, Kentucky, to Ron Cyrus, a Politician and former steelworker, and his wife, the former Ruth Ann Casto. Cyrus started singing at the age of four. His parents divorced in 1966. His grandfather was a Pentecostal preacher. Growing up, he was surrounded by bluegrass and gospel music from his family. His right-handed father played guitar however left-handed Cyrus tried to play his father's guitar, but could not. He attended Georgetown College on a baseball scholarship before changing to music. He dropped out of Georgetown during his junior year, realized he wanted to become a musician after attending a Neil Diamond concert, and set a 10-month goal to start a career. In the 1980s, he played in a band called Sly Dog, before signing a record contract with Mercury Nashville Records. Sly Dog was named after a one-eyed dog that Cyrus owned.

From 1986 to 1991, Cyrus was married to Cindy Smith, with whom he co-wrote the songs "Wher'm I Gonna Live?" and "Some Gave All", both of which were featured on his 1992 debut album Some Gave All.

While trying to get a recording contract in Los Angeles, Cyrus suffered many hardships including living in his neighbor's car. However, in 1990, he was signed to PolyGram/Mercury. That same year, he opened for Reba McEntire. Cyrus began to record and write music for his debut album, released in 1992.

Cyrus also has a son, Christopher Cody (born April 1992), from a previous relationship with Kristin Luckey, who raised him in South Carolina. In a 2004 interview on ABC News: Primetime, Cyrus stated that Miley (conceived with Finley) and Christopher (conceived with Luckey) were both born in 1992, when he was unmarried, and his marriage to Finley the following year (while she was pregnant with their son) was secret and against his record company's advice.

On December 28, 1993, Cyrus married Leticia "Tish" Cyrus (née Finley; born May 13, 1967). Together they have three children: Miley Cyrus (born as Destiny Hope in 1992), Braison Chance (born 1994), and Noah Lindsey (born 2000). He also has two adopted stepchildren from Finley's previous relationship: Brandi Cyrus (born 1987); and Trace Cyrus (born 1989), singer/guitarist for Metro Station. Cyrus adopted Brandi and Trace when they were young children.

Also in 1994, Cyrus contributed the song "Pictures Don't Lie" to the AIDS benefit album Red Hot + Country produced by the Red Hot Organization.

Cyrus' most critically acclaimed album was 1996's Trail of Tears on Mercury Records. The album debuted at No. 20 on the Country chart when released. Only two songs made the cut to radio, although neither one hit the top 60. The title track and "Three Little Words" reached No. 69 and No. 65 respectively. The album failed to reach any certification, and was on and off the charts after only four weeks.

In 1998, Cyrus released his last album for Mercury Records Shot Full of Love. The album became his lowest-peaking album, debuting at No. 32. The first single, "Under the Hood", failed to chart, "Time for Letting Go" hit No. 70, "Busy Man" charted No. 3, and "I Give My Heart to You" reached No. 41. After the single fell from the charts, Cyrus left Mercury's roster and signed with Monument Records in 1999.

Cyrus starred in the 1999 independent film Radical Jack. He also had a small part in David Lynch's 2001 film Mulholland Drive as Gene, a pool cleaner who had been having an affair with the wife of Adam Kesher (Justin Theroux). In 2001, Cyrus played the lead role on the PAX (now ION Television) comedy-drama Doc, which became the network's highest-rated show. In 2005, Cyrus expanded his acting career in a stage production of Annie Get Your Gun in Toronto, appearing in the role of Frank Butler.

Cyrus described himself as a "lifelong" Democrat in 2000, when his song "We the People" was being used as a campaign song by George W. Bush.

From 2001 to 2004, Cyrus starred in the television show Doc. The show was about a country Doctor who moved from Montana to New York City. From 2006 to 2011, he co-starred in the Disney Channel series Hannah Montana with his daughter Miley Cyrus. As of 2016, he stars as Vernon Brownmule on the CMT sitcom Still the King.

After the singles from Southern Rain finished their chart runs, Cyrus began to record two Christian albums. Both albums, Time Flies and The Other Side, were released in 2003. The first album debuted and peaked at a low No. 56 on the Country album charts. Three singles were released; however, only the final single charted. "Bread Alone", "What Else Is There", and "Back to Memphis" were released, and "Back to Memphis" charted to No. 60.

Cyrus' television credits include The Nanny, Diagnosis Murder, Love Boat, The Next Wave, and TNN's 18 Wheels Of Justice. In 2004, he guest-starred as a limo driver in the episode "The Power of Love" of the Canadian teen drama Degrassi: The Next Generation. Cyrus has also been the subject of many television specials that detail his rise to fame and his career. These include two ABC documentaries, Billy Ray Cyrus: Dreams Come True and Billy Ray Cyrus: A Year on the Road, a VH1 exclusive, as well as the TNN specials I Give My Heart To You, and The Life and Times of Billy Ray Cyrus. In late 2005, Cyrus and his daughter Miley Cyrus began co-starring in the Disney Channel original television series, Hannah Montana, which premiered on March 24, 2006.

In March 2007, Cyrus joined several other celebrities to take part in the fourth season of the US version of Dancing with the Stars. He and his partner Karina Smirnoff, were eliminated in the eighth week (May 8, 2007) after having also placed in the "bottom two" the week before.

On November 12, 2008, Billy Ray and Miley presented the "Song of the Year" award at the 42nd Annual Country Music Association Awards. Prior to the award show, both Billy Ray and Miley performed on Good Morning America. In December 2008, Cyrus made a cameo in Metro Station's video, "Seventeen Forever".

Cyrus, Phil Vassar, Jeffrey Steele, and John Waite then formed a new supergroup together in early 2009 called Brother Clyde. On Twitter, Cyrus confirmed the supergroup, saying they just cut the first single from the new album, Lately.

On October 26, 2010, Cyrus filed for divorce from his wife in Tennessee, citing irreconcilable differences. In a statement made to People the next day announcing the split, the couple said, "As you can imagine, this is a very difficult time for our family... We are trying to work through some personal matters. We appreciate your thoughts and prayers." However, on March 18, 2011, Cyrus announced on The View that he had dropped the divorce. On June 13, 2013, Tish filed for divorce from Billy Ray after 19 years of marriage, citing irreconcilable differences. However, it was reported in July 2013 that they had gone to couples therapy and rekindled their relationship.

In late 2010, Cyrus suspended his activities in the band Brother Clyde, and announced the release of his new solo patriotic album, entitled I'm American. Initially scheduled to be released in November 2010, it was pushed back to a May 24, 2011 release with a re-recording of "Some Gave All" that featured guest vocals from Darryl Worley, Jamey Johnson and Craig Morgan being released as the lead-off single. However, in April 2011, the single was changed to "Runway Lights". I'm American was released on June 28, 2011. A second single, "Nineteen", was released in August 2011. The song entered the Hot Country Songs chart for the week of October 8, 2011, where it debuted at number 58, becoming Cyrus' first charted single since "A Good Day" in 2009.

Cyrus released the album Change My Mind on October 23, 2012. Its first single, the title track, was released on September 6.

The second Christian album, The Other Side, was recorded while Cyrus filmed his PAX series, Doc. It debuted at No. 5 on the Top Christian Albums chart, No. 18 Top Country Albums, and No. 131 on Billboard 200. Two of three singles charted – "Face of God" (#54) and "The Other Side" (#45) – while "Always Sixteen" did not chart.